Evidence map›Paper›PMID 41176900›Full record

ArticleDrug and alcohol dependence2025

β-Nicotyrine and e-cigarette abuse liability I: Pharmacodynamics and interaction with pharmacokinetics and discriminative stimulus effects of nicotine in rats.

J R Smethells, S Wilde, P Muelken, J Vigliaturo, M D Raleigh, M Pravetoni, K J Kellar, T Olson, M G LeSage, A C Harris

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In one paragraph

Article in Drug and alcohol dependence, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

J R SmethellsHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA. Electronic address: smet0011@umn.edu.
S WildeHennepin Healthcare Research Institute, Minneapolis, MN, USA.
P MuelkenHennepin Healthcare Research Institute, Minneapolis, MN, USA.
J VigliaturoDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
M D RaleighDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
M PravetoniDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA; Department of Medicine, University of Washington, WA, USA.
K J KellarDepartment of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, USA.
T OlsonDepartment of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, USA.
M G LeSageHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
A C HarrisHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.

Funding

An evaluation of Beta-nicotyrine as a potential contributor to the abuse liability of e-cigarettesR01DA053608 · NIDA · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI SMETHELLS, JOHN RICHARD · 2021 to 2023
$989k
NIDA NIH HHS R01 DA053608
6 · The paper itself

Abstract

backgroundβ-Nicotyrine (β-Nic) is a prevalent minor alkaloid in electronic nicotine delivery systems (ENDS) aerosols. High doses of β-Nic slow nicotine (Nic) metabolism in mice, suggesting it may alter the abuse liability of ENDS. Thus, the present study examined the pharmacokinetics and pharmacodynamics of β-Nic and Nic, both alone and in combination, including the ability of β-Nic to produce nicotine-like discriminative-stimulus (i.e., subjective) effects and/or enhance the effects of Nic in rats. METHODS AND

resultsUnlike Nic and Nornicotine (Nornic) which bound to and activated acetylcholine receptors (α2β2, α3β4, α4β2) in vitro, β-Nic did not bind to these receptors, nor did it bind to a range of noncholinergic receptors (e.g., dopamine, GABA). A clinically relevant β-Nic dose (i.e., 25 % of Nic) slowed Nic clearance by ~50 %. In rats trained to discriminate Nic (0.2mg/kg) from Saline (Sal), β-Nic alone weakly substituted for Nic in females, but not males, whereas Nornic substituted for Nic in both sexes. Combinations of Nic + β-Nic increased the discriminability of Nic when administered 10- and 60-min prior to testing. Drug naïve rats learned to discriminate Nornic, but not β-Nic, from Sal.

conclusionsβ-Nic slows Nic clearance in rats and enhances and prolongs the discriminative stimulus effects of Nic, suggesting it may contribute to the abuse liability of ENDS.

Indexed as

Discrimination LearningDiscrimination, PsychologicalElectronic Nicotine Delivery SystemsNicotineNicotinic AgonistsAnimalsDose-Response Relationship, DrugFemaleMaleRatsRats, Sprague-DawleyReceptors, NicotinicNicotineNicotinic AgonistsReceptors, NicotinicBeta-nicotryineDrug discriminationMinor alkaloidsNicotineNicotine metabolismRat

Identifiers

PMID41176900
PMCPMC12794811

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.